Bioactive glass is a known bioactive and biocompatible material. For decades, bioactive glasses have been investigated as bone filling materials that can bond with bone, even chemically. Recent discoveries of the superior qualities of bioactive glasses have made the materials far more interesting for these applications. Certain bioactive glasses are commercially sold under the trade names of e.g. BonAlive®, NovaBone® and Biogran®. Bioactive glasses have been used in different forms for medical applications, such as granules and plates for orthopaedic and cranio-maxillofacial bone cavity filling and bone reconstruction. Certain bioactive glass formulations have been disclosed in the prior art e.g. EP 802 890 and EP 1 405 647. Some compositions of bioactive glasses are also known to have antimicrobial effects e.g. U.S. Pat. No. 6,190,643 and U.S. Pat. No. 6,342,207.
The main benefits of using bioactive glass as a bone graft substitute is that harvesting of the bone grafts from a secondary site can be avoided. Within a certain composition range bioactive glasses stimulate bone growth and show bacterial-growth inhibiting properties.
In order for the glass to be bioactive and have the above-mentioned properties the glass needs to dissolve and to have a certain dissolution rate as well as have certain composition. The relationship between the composition and the bioactivity has been described in Hench L. Bioactive ceramics: Theory and clinical applications. Bioceramics 1994; 7:3-14 in a way that gives a person skilled in the art sufficient tools to design a bioactive glass.
One factor influencing the dissolution rate and therefore the total degradation time of the glass particles is the particle size, or the surface area to volume ratio (A/V). In other words the smaller the particle the higher the A/V ratio and the faster the dissolution and the shorter the total degradation time. For example, the commercially available glass 45S5/Bioglass® is available in a size range from 90-710 μm and it is claimed to dissolve in the body in less than a year. Glass S53P4, sold under the trade name BonAlive®, has a chemical composition of 53 weight-% of SiO2, 23 weight-% of Na2O, 20 weight-% of CaO and 4 weight-% of P2O5, and it is a clearly slower dissolving glass than the 45S5 glass that has a composition of 45 weight-% of SiO2, 24.5 weight-% of Na2O, 24.5 weight-% of CaO, and 6 weight-% of P2O5.
In order to enhance the use and to broaden the surgical scope of bioactive glass, mouldable paste or putty types of compositions have been developed. In an ideal case, the putty formulation should be easily dosable, handable and directly administrable to the bone defect without risk of cross-contamination, spillage or excess dosage. In practice, physicians have used their hands in dosing and shaping of putty, and fingers and/or spatula or similar for filling the bone cavities. However, such a formulation possesses a number of practical disadvantages due to e.g. contamination risks during handling, which is not optimal for the patient or the physician.
One synthetic putty/paste formulation is known from US 2008/0226688 and is commercially known as NovaBone® Putty. This document describes a bone void filler type of paste or putty i.e. a sterile formable implant composition for application to a bone defect site comprising bioactive glass particles in an aqueous carrier solution. The bioactive glass particles are added to a viscous carrier at a concentration ranging from about 68% to about 76% (wt/wt). The carrier comprises a mixture of glycerol and polyethylene glycol (PEG) ranging from 24 to 32% (wt/wt) with the ratio of glycerol to polyethylene glycol ranging from about 45:55 to about 65:35.
However, this formulation possesses a number of practical disadvantages; Due to the physical and chemical characteristics and the ratios of the carriers and bioactive glass the material is not easily injectable. In addition, due to the relatively fast resorbing 4555/Bioglass® and the small powder and granule sizes, the formulation is only suitable for fast healing defects and is not suitable for long term bone growth applications. Moreover, the product viscosity is limited to certain applications only and is too high for injectable and syringe usage.
In addition to these disadvantages the risks of accidentally spilling grafting material into soft tissues while trying to reach the bone defect is significantly higher when not having the grafting material in an injectable form. A further disadvantage is that an extra tool e.g. a spatula is needed for the handling.
In addition to fully synthetic bone void filler putties or pastes, certain semi-synthetic mixtures in the form of putty or paste formulations, such as mixtures of allograft bones, demineralised bone matrix and bovine collagen/hydroxyapatite, have been in wide use and are known in the art. In addition, several patent documents on demineralised bone matrix compositions are known e.g. U.S. Pat. No. 5,073,373. Grafton® demineralised bone matrix (DBM) putty and gel bone void filler, bone graft extender and bone graft substitute have been provided for use in surgical bone repair. The composition disclosed in U.S. Pat. No. 5,073,373 is based on a demineralised bone powder in a biocompatible liquid carrier e.g. glycerol. Exactech Resorbable Bone Paste (US 2004/091462 is a mixture of demineralised bone matrix in a bioinert polyethylene glycol (PEG) based polymer and is provided as an aseptic product for single use, as a ready to use implantable device derived from a single donor. The demineralised bone matrix resorbs and is replaced with new bone during the healing process.
However, such allograft formulations possess a number of disadvantages of which the risk of transmission of disease is the largest disadvantage and can never be fully excluded.